STRUCTURING A FECAL MICROBIOTA TRANSPLANTATION CENTER IN A UNIVERSITY HOSPITAL IN BRAZIL.

BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

Estruturação de centro de transplante de microbiota fecal em hospital universitário no Brasil / Structuring a fecal microbiota transplantation center in a university hospital in brazil

ABSTRACT BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

RESUMO CONTEXTO: O Transplante de microbiota fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, poucos casos isolados de TMF foram relatados sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). OBJETIVO: O principal objetivo deste estudo foi descrever o processo de implantação de um CTMF com banco de fezes, em hospital universitário brasileiro, para tratamento de infecção recorrente e refratária pelo C. difficile. MÉTODOS: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o Food and Drug Administration, Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. RESULTADOS: Foi estabelecida toda uma plataforma envolvida na estruturação de um centro de transplante com fezes congeladas. Determinou-se os critérios para seleção de doadores, processamento e armazenamento de amostras, manejo dos receptores antes e após o procedimento, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção dos doadores foi conduzida em três etapas: pré-triagem, avaliação clínica e exames laboratoriais. Boa parte dos candidatos foram excluídos na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (IMC ≥25 kg/m2) e distúrbios gastrointestinais crônicos. Quatro dos 134 candidatos foram selecionados após a triagem completa, com taxa de detecção de doadores de 3%. CONCLUSÃO: A implantação de um CTMF, inédito no nosso meio, possibilita o acesso de pacientes com infecção recorrente e refratária pelo C. difficile a tratamento inovador, seguro, com elevada taxa de sucesso e pouco disponível no Brasil. A seleção apropriada de doadores qualificados é vital no processo de implantação de um CTMF. A avaliação clínica rigorosa dos doadores permitiu o uso racional de recursos para realização de exames laboratoriais. Um CTMF possibilita tratamento sob demanda, em maior escala, menos personalizados, com mais segurança e rastreabilidade. Este protocolo fornece subsídios para a realização de TMF em países emergentes.

Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey.

AIM: To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. METHODS: The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. RESULTS: Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. CONCLUSION: The H. pylori clarithromycin resistance rate in Brazil is at the borderline (15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate (13.5%) is equally concerning.